Peptide growth factors are multifunctional. They can either stimulate or inhibit cellular proliferation and function. One possible mechanism for this multifunctional action is cross-talk between the different receptor-- coupled effector systems. Such cross-talk exists because products from the phospholipase C and adenylate cyclase effector systems modulate one another. Our studies in fat cells as well as in leukocytes indicate the presence of such cross-talk. The direct addition of purified PKC stimulates adenylate cyclase activity in fat cells. Similarly, the level of adenylate cyclase activity is higher in PMA (a protein kinase C activator) treated cells. It has been suggested that one or more components of adenylate cyclase may serve as substrates for PKC. The most likely candidate would be the inhibitory GTP-binding protein (Gi). However, our studies indicate that although a number of plasma membrane proteins are phosphorylated by PKC, one phosphoprotein with an apparent molecular size of 41 KD seems to be similar to the Gi protein. The phosphorylated protein, however, is electrophoretically separated from Gi. Further confirmation for the lack of identity between the 41 KD PKC substrate and Gi was obtained with antibodies raised against a number of Gi proteins. The functional assays for GI, also support the above data, since pertussis toxin treated cells retain their ability to be activated by PKC. The results of this study were submitted to J.Biol.Chem as: Naghshineh, S., Huang, KP., and C. Londos., Protein kinase C activates adenylate cyclase by phosphorylation of a component other than the inhibitory GTP binding protein.